TCR-Vbeta flow cytometric analysis of peripheral blood for assessing clonality and disease burden in patients with T cell large granular lymphocyte leukaemia

J Clin Pathol. 2010 Feb;63(2):141-6. doi: 10.1136/jcp.2009.069336.

Abstract

Aims: T cell large granular lymphocytes (T-LGLs) are commonly increased in reactive conditions as well as T-LGL leukaemia. This differential diagnosis often requires a combined assessment of clonality and tumour burden. In this study we assessed the utility of flow cytometric (FC) analysis of T cell receptor beta chain variable region (TCR-Vbeta) expression by using 24 antibodies reactive to 70% of the TCR-Vbeta repertoire.

Methods: Analyses were performed on peripheral blood samples obtained from 20 patients with a confirmed diagnosis of T-LGL leukaemia and 18 patients without known T cell lymphoproliferative diseases.

Results: The results were compared with TCR gene rearrangement status assessed by PCR. By FC analysis, 19/20 T-LGL leukaemia cases were CD3+CD8+ and one case was CD3+CD4+. All the cases demonstrated at least one immunophenotypic aberration, with altered CD5 expression being most frequent. Abnormal Vbeta expression was detected by FC in 19 of 20 (95%) T-LGL leukaemia cases, but in none of the controls; this showed 100% concordance with TCR gene rearrangement studies. In addition to establishing clonality, FC Vbeta analysis enables calculation of absolute numbers of clonal T cells; this is important in monitoring tumour burden after treatment.

Conclusions: It is concluded that FC Vbeta analysis is a fast, reliable and quantitative method that can simultaneously assess T-LGL leukaemia clonality and tumour burden.

MeSH terms

  • Adult
  • Aged
  • CD4-CD8 Ratio
  • Female
  • Flow Cytometry / methods
  • Gene Rearrangement, beta-Chain T-Cell Antigen Receptor
  • Humans
  • Immunophenotyping
  • Leukemia, Large Granular Lymphocytic / genetics
  • Leukemia, Large Granular Lymphocytic / immunology*
  • Lymphocyte Subsets / immunology
  • Male
  • Middle Aged
  • Neoplastic Stem Cells / immunology
  • Receptors, Antigen, T-Cell, alpha-beta / blood*
  • Receptors, Antigen, T-Cell, alpha-beta / genetics
  • Young Adult

Substances

  • Receptors, Antigen, T-Cell, alpha-beta